br Conclusions and future directions

Conclusions and future directions
The combination of antipsychotic/s, galantamine and memantine may target dopaminergic, cholinergic and glutamatergic systems concurrently to improve cognitive improvements in schizophrenia (Buchanan et al., 2007; Geerts et al., 2015; Koola et al., 2014). Measuring KYNA and L-kynurenine concentrations could be the novel target engagement to measure the degree of cognitive impairment and to monitor prognosis with the treatment. There are ongoing studies to test this potassium channel blocker (clinicaltrials.gov identifier NCT02234752). More stringent inclusion and exclusion criteria on antipsychotics (Geerts et al., 2015), anticholinergic treatment (Geerts et al., 2015; Wijegunaratne et al., 2014), careful analysis of smoking status (Geerts et al., 2015), paying more attention to pharmacokinetics and pharmacodynamics and using SNPs to predict response may enable the field to detect clinically meaningful effectiveness signal. KYNA and L-kynurenine concentrations decrease with anti-inflammatory treatment. Future studies are warranted to examine specific SNPs that may predict response in the kynurenine pathway with the anti-inflammatory treatment.
<br>
Role of Funding Source
The manuscript preparation was supported by the NIMH-funded T32 grant MH067533-07 (PI: William T. Carpenter, MD).

Contributors

Conflict of Interest

Acknowledgements

Background
Social cognition (SC) is a psychological construct that refers to a collection of mental operations that underlie social interactions. SC includes the processes involved in the perception, interpretation and generation of responses when faced with the intentions, dispositions and behavior of others (Green et al., 2008; Penn, Sanna, and Roberts, 2008).
SC includes emotion perception, both in people’s faces and voices (Kohler et al., 2010; Tseng et al., 2013); social perception (Couture et al., 2006; Pinkham, 2014) i.e., the interpretation of clues about what happens in a certain social context and the application of this social understanding to develop more appropriate behavior; theory of mind (ToM) (Brüne, 2005b; Sarfati et al., 1999), which is defined as the ability to be aware that others have different ideas and intentions than ours; and attributive style (AS), which refers to people’s tendency to explain events that have occurred in their life and that sometimes leads them to consider the negative events as caused by the misconduct of others (Green et al., 2008; Hasson-Ohayon et al., 2014; Langdon et al., 2013; Mizrahi et al., 2008). In recent years, this topic has been the subject of intense study, revealing disorders in emotion perception, ToM, AS and social perception in patients with schizophrenia (Chung et al., 2014; Kurtz and Richardson, 2012; Lahera et al., 2014; Savla et al., 2013). The study of these deficits and of strategies for improving them is important because SC appears to have a greater repercussion on social function than neurocognition itself (Bigelow et al., 2006; Brüne, 2005a; Green et al., 2008) and is considered to be a mediator between neurocognition and functional performance (Casacchia et al., 2004; Penn et al., 1996; Pinkham and Penn, 2006). SC rehabilitation has been made possible by various therapeutic models (Addington et al., 2006; Addington et al., 2010). These rehabilitation models initially focused on the construct’s specific subdomains (Combs et al., 2009; Frommann et al., 2003; Kayser et al., 2006; Penn and Combs, 2000; Roberts and Penn, 2009; Roder, Mueller, and Schmidt, 2011; Russell et al., 2006; Silver et al., 2004). More ambitious models subsequently emerged that included all components of SC (Horan et al., 2009; Roberts et al., 2014; Rocha and Queirós, 2013). However, all of these models required a significant number of sessions (between 12 and 45), were typically applied in a group setting and required specific training by the therapists, factors that hindered their application in the clinical setting (Roberts et al., 2010). With this objective in mind, we designed an online rehabilitation program for SC, limited to just 12 sessions (the minimum number of face-to-face sessions reported in previous studies.)